The coupling between clonal modes of reproduction and hybridization in unisexual vertebrates has led to the hypothesis that heterosis accounts for their ecological success (the "spontaneous heterosis" hypothesis). High levels of genic heterozygosity characteristic of unisexual-hybrid vertebrates are believed to result in enhanced growth, survivorship, and fertility relative to their sexual ancestors. To test this hypothesis, we synthesized 33 new unisexual-hybrid strains of fishes in the genus Poeciliopsis (Atheriniformes: Poeciliidae). On average, the synthetic unisexuals had lower survivorship and a higher incidence of birth defects than either of the sexual ancestors or two natural strains of unisexuals. However, a subset of these synthetic unisexuals exhibited characteristics within the range of the sexual ancestors and natural unisexual strains. These results support the alternative hypothesis that the ecological success of natural unisexuals results from selection of the most fit clones from a broad spectrum of genotypes that arose via multiple hybrid events. We propose that the coupling between unisexuality and hybridization in the vertebrates exists because hybridization is a dysgenic process that can disrupt normal gametogenesis and thus lead to clonal reproduction.

During the past decade, the pharmaceutical industry has seen the increasing application of pharmacometrics approaches in drug development. However, the full potential of incorporating model-based approaches in drug development and its impact on decision making has not been fully realized to date. In 2009, a survey on model-based drug development (MBDD) was conducted (1) to further understand the current state of MBDD in the pharmaceutical industry and (2) to identify opportunities to realize the full potential of MBDD. Ten large and mid-sized pharmaceutical companies provided responses to this survey. The results indicate that MBDD is achieving broad application in early and late development and is positively affecting both internal and regulatory decisions. Senior leadership (vice president and higher) within the companies indicated widely accepted utility for dose selection and gaining acceptance for study design and regulatory interactions but limited acceptance in discovery and commercial/pipeline decisions. Mounting appreciation for the impact of MBDD on internal and regulatory decision-making bodes well for the future of the pharmacometric discipline and the growth of opportunities to realize the full potential of MBDD.

No abstract

The frozen-niche-variation model was proposed to account for the coexistence of genetically related clones in naturally occurring unisexual populations. This model is based on two assumptions: 1) ecologically different clones have multiple independent origins from sexual ancestors; and 2) the population of sexual ancestors contains genetic variability for ecologically relevant traits. To test these assumptions, we produced 14 new "hemiclones" (nonrecombining haploid genotypes) of fish (Poeciliopsis: Poeciliidae). Our ability to synthesize many new hemiclones demonstrates the feasibility of multiple independent origins of nonrecombining genotypes. A substantial proportion (10-50%) of the phenotypic variation among hemiclones in size at birth, juvenile growth rate, and fecundity had a genetic basis. Thus, we conclude that multiple origins can give rise to an assemblage of genetically distinct hemiclones, each with a unique combination of life-history traits. Additionally, a comparative analysis of two natural hemiclones revealed that the synthetic strains represent a broad field of variation from which natural hemiclones can be selected.